The objective of this research is to study selected etiologic questions about the bipolar and unipolar forms of affective disorder. The Old Order Amish population serves as an ideal type of human laboratory to determine homogeneous sub-samples of types of affective disorder and for establishing heritability. The Project is studying data from multigenerational pedigrees with large sibships of confirmed bipolar and unipolar probands. Clinical work will seek linkage with a variety of marker traits (biochemical and hematological parameters) and these data will be subjected to linkage analysis. Also, pedigree analysis will be done to test hypotheses regarding the mode of genetic inheritance. Another objective of the research is to consider selected behavioral and environmental factors in the pathogenesis of affective disorders. Affectively disturbed individuals and their unaffected relatives will be compared according to demographic, behavioral and symptomatic data. These putative factors will be examined to question why the illness is manifest in given individuals who may share a common genetic predisposition with other well relations. The long-term goal of these various objectives is to clarify questions about the causation (etiology) and classification (diagnosis) of affective disorder.